1. ANTIBIOTICS
(Foundation Block, Microbiology)

2. Lecture Objectives..
By the end of this lecture the student should be able to:
Define antibiotic ,chemotherapy and selective toxicity
Describe the difference between bactericidal and bacteriostatic antibiotics
Recognize the narrow and broad spectrum antibiotics
Define the therapeutic index

3. Lecture Objectives..
Know the mechanism of action of antimicrobial agents.
Recognize the various classes of antimicrobial agents(action, spectrum and side effects)
Explain the criteria for an ideal antimicrobial

4. ANTIMICROBIAL AGENTS ANTIBIOTICS:
Natural compounds produced by microorganism which inhibit the growth of other microorganism .
CHEMOTHERAPY:
Synthetic compounds .
Antimicrobial agents.

5. SELECTIVE TOXICITY:
The ability to kill or inhibit the growth of a microorganism without harming the host cells.

6. THERAPEUTIC INDEX:
The RATIO of the dose toxic to the host to the effective therapeutic dose.
Examples:
Penicillin: High
Aminoglycosides : low
Polymyxin B : the lowest

7. Activity
BACTERICIDAL: kills bacteria
BACTERIOSTATIC: prevents multiplication.
Spectrum of activity
Broad spectrum : Gram positive & Gram negative bacteria
Narrow spectrum : selected organism.

9. MECHANISMS OF ACTION OF ANTIMICROBIALS
1) Inhibition of cell wall synthesis.
2) alteration of cell membrane
3) Inhibition of protein synthesis
4) Inhibition of nucleic acid synthesis
5) Anti-metabolite OR competitive antagonism.

14. ANTIMICROBIALS THAT INHIBIT CELL WALL SYNTHESIS
1- Beta –Lactam antimicrobial agents
Penicillins
Cephalosporins
Cephamycin
Carbapenems ( imipenem & meropenem)
Monobactam (aztreonam)
Beta-lactamase inhibitors
2- Vancomycin ( Teicoplanin )

15.  - LACTAM ANTIBIOTICS:
Contain : Beta- Lactam ring & organic acid.
Natural & Semi-synthetic
Bactericidal
Bind to PBP, interfere with trans-peptidation reaction
Toxicity: mainly;
hypersensitivity
Anaphylaxis ,
Diarrhea, ..etc

18. Isoxazolyl penicillins : cloxacillin – Staph.
Benzyl penicillin –
- Penicillin V
Procaine penicillin
Benzathine penicillin
Isoxazolyl penicillins : cloxacillin – Staph.
Amino-penicillins -ampicillin –Enterobacteria.
Acylaminopenicillins: piperacillin,mezlocillin Psudomonas.

19. CEPHALOSPORINS:
First Generation:
Cephradine
Ceohalexine
Second generation:
Cefuroxime
Cephamycin (Cefoxitin)
Third generation:
expanded spectrum
eg. Ceftriaxone
Ceftazidime
Fourth generation:
Cefepim
Ceftobiprole

20. β-Lactamase inhibitors
β-Lactams with no antibacterial activity
Irreversibly bind to β-lactamase enzyme
Clavulanic acid, Sulbactam, Tazobactam
Effective on staph. Penicillinases and broad spectrum β-lactamases.
eg. amoxicillin/clavulanic acid, ticarcillin /clavulanic acid and piperacillin /tazobactam.

24. VANCOMYCIN Glycopeptides
Bactericidal .Acts on Gram positive bacteria only.
Inhibit cell wall synthesis
Given by injection only.
Used for MRSA ,S.epidermidis, pseudomembranous colitis.
Red man syndrome ,phlebitis, nephrotoxic & ototoxic.

25. ANTIBIOTICS THAT ALTER CELL MEMBRANES
Polymyxin B and Colistin
Polymyxin B :a Peptide active against Gram negative bacteria only.
Bactericidal.
Only used LOCALLY due to serious nephrotoxicity
Colistin used for the treatment of multi-resistant organisms (MRO) such as :Pseudomonas and Acinetobacter infections.

26. ANTIBIOTICS THAT INHIBIT PROTIEN SYNTHESIS
AMINOGLYCOSIDES S30S ribosomal subunit
TETRACYCLINE S30S ribosomal subunit
CHLORAMPHENICOL 50 Sub Unit of 23 r RNA
MACROLIDES Sub Unit of 23 r RNA

28. Acts only on Gram negative bacteria
AMINOGLYCOSIDES:
Bactericidal
Acts only on Gram negative bacteria
Streptococci & anaerobes are naturally resistant
Examples: Gentamicin ,Amikacin , Neomycin ,
Given by injection .
Nephrotoxic & Ototoxic - dose related.

29. TETRACYCLINES
Broad spectrum , bacteriostatic
Oral absorption
Intracellular organisms eg. Mycoplasma, Chlamydia ,Brucella also for V. cholera & Nocardia
Classes:
Short acting: Tetracycline
Long acting: Minocycline , Doxycycline ( CSF penetration).
New tetracycline : Tigycycline ( MRSA,MSSA, some Gram negative bacteria and anaerobes.
Side effects :
Teeth discoloration , GIT disturbance

30. Broad spectrum ,bactericidal
CHLORAMPHENICOL
Broad spectrum ,bactericidal
Affects bone marrow cells and cause a plastic anemia
Used for severe infections not responding to treatment , also for Rickettsial diseases.

31. MACROLIDES: Erythromycin & Clindamycin Bacteriostatic
Legionella, Camylobacter, Gram negative and positive infections for patients allergic to Penicillins and Cephalosporins.
Clindamycin acts on anaerobes as well
Cause GIT disturbance, Pseudomembraneous colitis.
New Macrolides :
Azithromycin & Clarithromycin .

32. ANTIMICROBIALS THAT ACT ON NUCLEIC ACID
Rifampicin
Quinolones
Metronidazole

33. RIFAMPICIN:
Semi-synthetic, bactericidal , acts on Gram positive bacteria and selected Gram negative bacteria.
Reserved for Tuberculosis
Resistance develops quickly
Used in combination
Causes discoloration of body fluids & hepatotoxicity

34. Synthetic, bactericidal, inhibit DNA Gyrase and /or topoisomerase.
QUINOLONES:
Synthetic, bactericidal, inhibit DNA Gyrase and /or topoisomerase.
Generations:
first generation: nalidexic acid –locally acting
Second generation: fluoroquinolones eg. ciprofloxacin, norfloxacin, ofloxacin,levofloxacin
Third generation: sparfloxacin, gatifloxacin
Fourth generation: moxifloxacin, trovafloxacin
Side effects: on cartilage & heart

35. Metronidazole
Nitroimidazole active on anaerobic bacteria, and parasite
Caused DNA breakage
Used for B.fragilis , Trichomonas vaginalis , amoebiasis and giardiasis.

36. ANTIMETABOLITES ( folate inhibitor s):
Trimethoprim-Sulfamethoxazole ( TMP-SMX)
Combination of TMP-SMX called : Bactrim / Septrin
Block sequential steps in folic acid synthesis
Used to treat :Nocardia, Chlamydia, Protozoa & P.cranii
UTI, LRTI, OM., Sinusitis, infectious diarrhea.
Side effects: GIT, hepatitis , bone marrow depression, hypersensitivity

38. ANTITUBERCULOUS AGENTS
First line:
- INH
RIFAMPICIN
ETHAMBUTOL
PYRAZINAMIDE
Second line:
STREPTOMYCIN
PASA
CYCLOSERINE,
CAPREOMYCIN

39. ISONIAZIDE (INH)
Bactericidal
Affects mycobacteria at different sites of lung tissues
Used for the treatment & prophylaxis of tuberculosis
Cause peripheral neuritis( pyridoxine (vitamin B6)

40. ACID ENVIRONMENT OF MACROPHAGES
Pyrazinamide
ACID ENVIRONMENT OF MACROPHAGES
HEPATITIS & ARTHRALGIA
Ethambutol
BACTERICIDAL
CONCENTRATED IN PHAGOLYSOSOME OF ALVEOLI
OPTIC NEURITIS

41. ANTIBIOTIC RESISTANCE IN BACTERIA
INDISCRIMINATE USE OF ANTIMICROBIALS
SELECTIVE ADVANTAGE OF ANTIBIOTICS
TYPES OF RESISTANCE:
PRIMARY:
Innate eg. Streptococcus & anaerobes are resistant to gentamicin.

42. ANTIBIOTIC RESISTANCE IN BACTERIA (Continue)
Acquired resistance :
1- MUTATION: MTB RESISTANT TO SRTEPTOMYCIN
2- GENE TRANSFER: plasmid mediated or through transposons
Cross resistance :
Resistance to one group confer resistance to other drug of the same group .
eg. Resistance to erythromycin and clindamycin
Dissociate resistance:
resistance to gentamicin does not confer resistance to tobramicin .

43. MECHANISMS OR RESISTANCE
1- Permeability changed
2- modification of site of action, eg. MUTATION
3- inactivation by enzymes . eg. Beta- Lactamase & aminoglycoside inactivating enzymes
4- passing blocked metabolic reaction eg. PABA folic acid , plasmid mediated.

44. PRINCIPLES OF ANTIMICROBIAL THERAPY:
INDICATION
CHOICE OF DRUG
ROUTE
DOSAGE
DURATION
DISTRIBUTION
EXCRETION
TOXICITY
COMBINATION
PROPHYLAXIS:
SHORT TERM:
MENINGITIS
LONG TERM:
TB, UTI , RHEUMATIC FEVER

45. CRITERIA FOR IDEAL ANTIMICROBIAL:
SELECTIVE TOXICITY
NO HYPERSENSITIVITY
PENETERATE TISSUES QUICKLY
RESISTANCE NOT DEVELOP QUICKLY
NO EFFECT ON NORMAL FLORA
BROAD SPECTRUM

46. Reference book and the relevant page numbers..
Sherries Medical Microbiology, an introduction to Infectious Diseases. Latest edition, Kenneth Ryan and George Ray. Publisher: Mc Graw Hill.

49. Thank You 
(Foundation Block, Microbiology)